ACE activity is modulated by the enzyme alpha-galactosidase A

Autor(es):Mostrar menos -

Batista, Elice Carneiro ; Carvalho, Luiz Roberto ^[1] ; Casarini, Dulce Elena ^[2] ; Carmona, Adriana Karaoglanovic ; dos Santos, Edson Lucas ^[3] ; da Silva, Elton Dias ; dos Santos, Robson Augusto ^[4] ; Nakaie, Clovis Ryuichi ; Munoz Rojas, Maria Veronica ^[5] ; de Oliveira, Suzana Macedo ; Bader, Michael ^[6] ; D'Almeida, Vania ^[7] ; Martins, Ana Maria ^[8] ; Souza, Kely de Picoly ^[3] ; Pesquero, Joao Bosco ^[9]

Afiliação do(s) autor(es)

^[1] Hosp Sao Vicente de Paulo, Dept Nephrol, Passo Fundo - Brazil

^[2] Univ Fed Sao Paulo, Dept Med, Div Nephrol, BR-04023062 Sao Paulo - Brazil

^[3] Fed Univ Grande Dourados, Sch Environm & Biol Sci, Dourados, MS - Brazil

^[4] Univ Fed Minas Gerais, Dept Physiol & Biophys, Belo Horizonte, MG - Brazil

^[5] Genzyme Brasil, Personalized Genet Hlth, Sao Paulo - Brazil

^[6] Max Delbruck Ctr Mol Med MDC, D-13125 Berlin - Germany

^[7] Univ Fed Sao Paulo, Dept Biosci, BR-04023062 Sao Paulo - Brazil

^[8] Univ Fed Sao Paulo, Dept Pediat, BR-04023062 Sao Paulo - Brazil

^[9] Univ Fed Sao Paulo, Dept Biophys, Escola Paulista Med, BR-04023062 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF MOLECULAR MEDICINE-JMM; v. 89, n. 1, p. 65-74, JAN 2011.
• Citações Web of Science: 8

Resumo

Fabry disease is a multisystem X-linked disorder resulting from alpha-galactosidase A (alpha-GalA) gene mutations leading to the accumulation of globotriaosylceramide mainly in endothelium compromising heart, kidney, and brain. In Fabry patients, progressive renal failure is frequently treated with angiotensin I-converting enzyme (ACE) inhibitors. We were interested in the possible interactions between ACE inhibitors therapy and the only causative therapy for Fabry disease, the enzyme replacement therapy (ERT) using recombinant human alpha-GalA (rh alpha-GalA). Our results suggest that ACE activity was significantly inhibited in plasma of Fabry patients and the blood pressure level decreased just after ERT (at the end of the rh alpha-GalA infusion). Interestingly, 2 weeks later, ACE activity was significantly upregulated and the plasma levels of angiotensin II increased in the patients treated with rh alpha-GalA following the elevations of ACE activity. The same inhibitory effect on ACE activity was also observed in rats after rh alpha-GalA infusion. Furthermore, ACE activity in CHO cells transfected with the human ACE was inhibited dose and time-dependently by rh alpha-GalA. In vitro, the incubation of plasma from healthy volunteers with rh alpha-GalA significantly reduced ACE activity. Finally, rh alpha-GalA also inhibited ACE activity and released galactose residues from purified rabbit lung ACE dose-dependently. In summary, our results suggest that rh alpha-GalA interacts with ACE and inhibits its activity, possibly by removing the galactose residues from the enzyme. This modulation might have profound impact on the clinical outcome of Fabry patients treated with rh alpha-GalA. (AU)

• Processo FAPESP: 08/06676-8 - Biologia celular e molecular dos sistemas calicreínas-cininas e renina-angiotensina
• Beneficiário: João Bosco Pesquero
• Modalidade de apoio: Auxílio à Pesquisa - Temático